Drug Interactions between ivacaftor / lumacaftor and maribavir

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of maribavir, which is primarily metabolized by the isoenzyme. When maribavir (400 mg twice daily) was administered with the potent CYP450 3A4 inducer, rifampin (600 mg once daily), maribavir peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 39% and 60%, respectively. Reduced virologic response to maribavir may occur.

MANAGEMENT: Concomitant use of maribavir with potent CYP450 3A4 inducers is not recommended. Alternative agents with lesser or no CYP450 3A induction potential should be considered whenever possible. If coadministration with potent CYP450 3A inducers cannot be avoided, a dosage increase of maribavir up to 1,200 mg twice daily has been suggested by some authorities.

Coadministration with inhibitors of the isoenzyme CYP450 3A4 may increase the plasma concentrations and effects of maribavir, a CYP450 3A4 substrate. When a single 400 mg dose of maribavir was administered with a single 400 mg dose of ketoconazole, a potent CYP450 3A4 and P-glycoprotein (P-gp) inhibitor, mean maribavir peak plasma concentration (Cmax) and total systemic exposure (AUC) increased by 10% and 53%, respectively, in 19 study subjects. These changes are not considered clinically significant. No dosage adjustments are necessary when maribavir is prescribed with CYP450 3A4 inhibitors, but it may be advisable to monitor patients for maribavir-related adverse effects such as taste disturbances, nausea, diarrhea, vomiting, and fatigue.